crossing96/oncoscreening huggingface dataset:
Utility of lymphadenectomy in bladder cancer: where do we stand?	PURPOSE OF REVIEW: The aim of this review is to provide insight into the current state of lymph node dissection (LND) during radical cystectomy in patients with bladder cancer (BCa). RECENT FINDINGS: The first prospective, multicenter, randomized, phase III trial to assess the therapeutic benefit of extended versus limited LND at the time of radical cystectomy failed to demonstrate relevant improvement with extended LND, but showed that this approach does not increase overall complications. Although contemporary rate of LND during radical cystectomy has increased, it remains suboptimal. Minimally invasive radical cystectomy with LND is feasible in most patients and has similar lymph node yields and complication rates compared with open procedures when performed by experienced surgeons. Overall major complication, readmission and mortality rates do not significantly differ according to extent of LND. SUMMARY: Meticulous LND provides both diagnostic and potentially therapeutic benefits in patients with bladder cancer. Results of ongoing trials will provide additional insights regarding the anatomic extent and therapeutic benefit of extended versus standard true pelvic-only LND.	bladder
The impact of low- versus high-intensity surveillance cystoscopy on surgical care and cancer outcomes in patients with high-risk non-muscle-invasive bladder cancer (NMIBC).	PURPOSE: To assess the association of low- vs. guideline-recommended high-intensity cystoscopic surveillance with outcomes among patients with high-risk non-muscle invasive bladder cancer (NMIBC). MATERIALS & METHODS: A retrospective cohort study of Veterans Affairs patients diagnosed with high-risk NMIBC between 2005 and 2011 with follow-up through 2014. Patients were categorized by number of surveillance cystoscopies over two years following diagnosis: low- (1-5) vs. high-intensity (6 or more) surveillance. Propensity score adjusted regression models were used to assess the association of low-intensity cystoscopic surveillance with frequency of transurethral resections, and risk of progression to invasive disease and bladder cancer death. RESULTS: Among 1,542 patients, 520 (33.7%) underwent low-intensity cystoscopic surveillance. Patients undergoing low-intensity surveillance had fewer transurethral resections (37 vs. 99 per 100 person-years; p<0.001). Risk of death from bladder cancer did not differ significantly by low (cumulative incidence [CIn] 8.4% [95% CI 6.5-10.9) at 5 years) vs. high-intensity surveillance (CIn 9.1% [95% CI 7.4-11.2) at 5 years, p = 0.61). Low vs. high-intensity surveillance was not associated with increased risk of bladder cancer death among patients with Ta (CIn 5.7% vs. 8.2% at 5 years p = 0.24) or T1 disease at diagnosis (CIn 10.2% vs. 9.1% at 5 years, p = 0.58). Among patients with Ta disease, low-intensity surveillance was associated with decreased risk of progression to invasive disease (T1 or T2) or bladder cancer death (CIn 19.3% vs. 31.3% at 5 years, p = 0.002). CONCLUSIONS: Patients with high-risk NMIBC undergoing low- vs. high-intensity cystoscopic surveillance underwent fewer transurethral resections, but did not experience an increased risk of progression or bladder cancer death. These findings provide a strong rationale for a clinical trial to determine whether low-intensity surveillance is comparable to high-intensity surveillance for cancer control in high-risk NMIBC.	bladder
Functional outcomes obtained with intracorporeal neobladder after robotic radical cystectomy for cancer: a narrative review.	Robot-assisted radical cystectomy with intracorporeal urinary diversion is one of the most challenging procedures in urological surgery. Over the past 15 years, this procedure has gained in popularity and the number of procedures performed has increased significantly. While ileal conduit remains the most common diversion, orthotopic neobladders are also formed in a few expert centres that have developed their technique for totally intracorporeal neobladder. The objective of this review is to summarise the techniques currently used to perform totally intracorporeal neobladder with a special focus on their functional outcomes, such as continence or sexual function. The techniques described are the Karolinska-modified Studer neobladder, the USC-modified Studer neobladder, the pyramid pouch, the Y-pouch, and the vesica Ileale Padovana, some trying to totally reproduce the steps of open surgery and others trying to simplify them. Functional outcomes vary depending on the technique performed. Standardisation in assessing outcomes is lacking, as well as objective outcome measurements with questionnaires or urodynamic assessments. Current evidence shows acceptable functional outcomes after totally intracorporeal neobladder construction, but larger prospective randomised series with longer follow-up, better defined outcomes, and more objective measurements are needed in the future.	bladder
Comparative genomic profiling of glandular bladder tumours.	"Primary glandular bladder tumours (bladder adenocarcinoma [BAC], urachal adenocarcinoma [UAC], urothelial carcinoma with glandular differentiation [UCg]) are rare malignancies with histological resemblance to colorectal adenocarcinoma (CORAD) in the majority of this subgroup. Definite case numbers are very low, molecular data are limited and the pathogenesis remains poorly understood. Therefore, this study was designed to complement current knowledge by in depth analysis of BAC (n = 12), UAC (n = 13), UCg (n = 11) and non-invasive glandular lesions (n = 19). In BAC, in addition to known alterations in TP53, Wnt, MAP kinase and MTOR pathway, mutations in SMAD4, ARID1A and BRAF were identified. Compared to published data on muscle invasive bladder cancer (BLCA) and CORAD, UCg exhibited frequent ""urothelial"" like alterations while BAC and UAC were characterised by a more ""colorectal"" like mutational pattern. Immunohistochemically, there was no evidence of DNA mismatch repair deficiency or PD-L1 tumour cell positivity in any sample. Depending on the used antibody 0-45% of BAC, 0-30% of UCg and 0% UAC cases exhibited PD-L1 expressing tumour associated immune cells. A single BAC (9%, 1/11) showed evidence of ARID1A protein loss, and two cases of UCg (20%, 2/10) showed loss of SMARCA1 and PBRM1, respectively. Taken together, our data suggest at least in part involvement of similar pathways driving tumourigenesis of adenocarcinomas like BAC, UAC and CORAD independent of their tissue origin. Alterations of TERT and FBXW7 in single cases of intestinal metaplasia further point towards a possible precancerous character in line with previous reports."	bladder
Carcinogen Biomarkers in the Urine of Electronic Cigarette Users and Implications for the Development of Bladder Cancer: A Systematic Review.	CONTEXT: Use of electronic cigarettes (e-cigarettes) has rapidly increased despite unclear longitudinal health effects. Once thought to be a safer alternative to tobacco smoke, it is possible that e-cigarettes expose the user to similar carcinogenic byproducts during the vaping process. These toxicants are metabolized and excreted in the urine, and may have oncogenic implications for bladder urothelium. OBJECTIVE: To characterize and summarize known urinary carcinogenic biomarkers in e-cigarette users as they relate to the risk of developing bladder cancer. EVIDENCE ACQUISITION: A systematic literature search was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and included PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL). Relevant articles published in peer-reviewed journals, through January 2019, that reported on urinary biomarkers in e-cigarettes users were included. Parent compounds and urinary biomarkers were classified according to the International Agency for Research on Cancer Monographs on the Evaluation of Carcinogenic Risks to Humans and cross referenced using the Collaborative on Health and the Environment, Toxicant and Disease Database to determine a link to bladder cancer, grouped by strength of evidence. EVIDENCE SYNTHESIS: Our initial search identified 1385 articles, 22 of which met final inclusion criteria and were included for analysis. In summation, these studies described 40 different parent compounds and four metals found in the urine of e-cigarette users. Since each parent compound can be metabolized several different ways, 63 unique toxicant or carcinogenic metabolite biomarkers were identified. Compared with nonuser controls, e-cigarette users had higher concentrations of urinary biomarkers of several carcinogenic compounds linked to bladder cancer. The majority of studies were limited by heterogeneous reporting and a dearth of control individuals who had never smoked. CONCLUSIONS: Biomarkers of carcinogens, several with a strong link to bladder cancer, are present in the urine of e-cigarette users. Long-term implications of urothelial exposure to these toxicants are unknown but concerning, given the similarities to tobacco smoke and its established relationship with bladder cancer. Further study on the urological safety of e-cigarettes is necessary. PATIENT SUMMARY: Our review shows that several carcinogens that have a known link to bladder cancer are present in the urine of electronic cigarette (e-cigarette) users. Further study on the urological safety of e-cigarettes is necessary.	bladder
Can robotic-assisted radical cystectomy provide patients with a smaller trauma and faster recovery period? A systematic review and meta-analysis of comparative trials.	OBJECTIVE: This article explores the differences in the effectiveness and safety of the treatment of bladder cancer (BC) by robotic-assisted radical cystectomy (RARC) and laparoscopic radical cystectomy (LRC). METHODS: A systematic search was performed using databases including Medline, PubMed and Web of Science within a limited period from January 1, 2000, to September 1, 2019. RevMan 5.3 was used for calculation and statistical analyses. RESULTS: We performed meta-analysis on operation time, estimated blood loss, intraoperative blood transfusion, positive surgical margin, oral intake time, length of hospital stay, complication and other indicators, and found that there were no statistically significant differences between LRC and RARC. CONCLUSION: Our meta-analysis results show that LRC and RARC have similar results on the effectiveness and safety of BC. For those medical institutions that cannot perform robot-assisted surgery but are seeking minimally invasive and faster postoperative recovery, LRC is worth considering. However, a larger sample size, more rigorous design and longer follow-up randomized controlled trials are still needed to support our conclusions.	bladder
CircRNA_0058063 functions as a ceRNA in bladder cancer progression via targeting miR-486-3p/FOXP4 axis.	Emerging evidence has uncovered critical regulatory roles of circular RNAs (circRNAs) function as dynamic scaffolding molecules in tumorigenesis and progression. However, the aberrant expression and clinical significance of hsa_circ_0058063 (circRNA_0058063) in bladder cancer (BC) remain poorly understood. circRNA expression was analyzed via a microarray in cancerous tissue and non-carcinoma tissues. Luciferase reporter assays and RNA immunoprecipitation (RIP) were both conducted to uncover the function of circRNA_0058063 in BC. circRNA_0058063 was overexpressed in BC tissues compared with adjacent normal tissues. Knockdown of circRNA_0058063 dramatically decreased cell proliferation and invasion, and promoted apoptosis in 5637 and BIU-87 cell lines. Furthermore, mechanistic investigations showed that circRNA_0058063 and FOXP4 could directly bind to miR-486-3p, demonstrating that circRNA_0058063 regulated FOXP4 expression by competitively binding to miR-486-3p. Taken together, circRNA_0058063 functions by sponging miR-486-3p in BC progression, which could act as a new biomarker and further developed to be a therapeutic target in BC.	bladder
Ultrasound-mediated nanobubble destruction (UMND) facilitates the delivery of VEGFR2-targeted CD-TK-loaded cationic nanobubbles in the treatment of bladder cancer.	BACKGROUND: The CD-TK double suicide gene has become an effective therapy for bladder cancer. A novel molecular-targeted ultrasound (US) method has been developed to precisely guide nanobubbles loaded with this gene to regions within bladder tumor cells and is widely used due to its efficiency in delivering drugs to the target tumor. METHODS: Uniform nanoscaled nanobubbles loaded with CD-TK double suicide gene were developed using a thin-film hydration sonication, carbodiimide chemistry approaches, and electrostatic adsorption methods. RESULTS: In the present study, we synthesized CD-TK double suicide gene-loaded cationic nanobubbles conjugated with anti-VEGFR2 that can bind with VEGFR2-positive cells. Fluorescence and flow cytometry evidence show that CD-TK double suicide gene-loaded nanobubbles were successfully developed. CD-TK-CNBs delivered via US-mediated nanobubble destruction (UMND) enhanced transfection efficiency, overexpression of CD-TK double suicide gene, and tumor cell apoptosis, and inhibited tumor cell growth in vitro. CONCLUSIONS: These CD-TK-CNBs may become a novel treatment for bladder cancer.	bladder
Central Nervous System Metastasis in Patients With Urothelial Carcinoma: Institutional Experience and a Comprehensive Review of the Literature.	"INTRODUCTION: Central nervous system (CNS) metastasis in patients with urothelial carcinoma (UC) is uncommon and poorly understood. We aimed to explore the clinical behavior and outcomes of this unique patient population. MATERIALS AND METHODS: We performed a retrospective analysis of patients with UC and CNS metastasis, treated in our institution (2006-2018), along with an exploratory patient-point meta-analysis of a similar patient population derived from a comprehensive literature review. Data regarding diagnosis, management, and outcomes were extracted. Overall survival, time to CNS metastasis (TTCM), and residual survival (RS) from CNS involvement to death were calculated (Kaplan-Meier method). Cox regression was used for testing key clinicopathologic associations. RESULTS: We identified 20 ""institutional"" and 154 ""literature"" patients with adequate data granularity for analysis. Median TTCM was 17.7 (institutional cohort) and 10 (literature cohort) months. Most patients who developed CNS metastases had previous non-CNS metastasis (15/20 [75%] and 103/154 [67%], respectively). CNS lesions without previous history of metastasis were identified in 5/20 (25%) and 33/154 (21%) cases and those patients had a shorter TTCM. CNS lesions in the absence of known UC history were also documented in 18/154 (12%) literature cases. Multifocal CNS disease was associated with shorter RS in both cohorts in univariate, but not multivariate, analysis. CONCLUSION: We observed a variability in disease presentation and course, with a subset of patients showing an early predilection for CNS insult, potentially reflecting a diverse underlying biology. Genomic profiling studies, elucidating the molecular landscape, and driving future treatments should be considered in this setting."	bladder
Blockage of O-linked GlcNAcylation induces AMPK-dependent autophagy in bladder cancer cells.	BACKGROUND: High levels of the post-translational modification O-GlcNAcylation (O-GlcNAc) are found in multiple cancers, including bladder cancer. Autophagy, which can be induced by stress from post-translational modifications, plays a critical role in maintaining cellular homeostasis and regulating tumorigenesis. The impact of O-GlcNAcylation on autophagy in bladder cancer remains unclear. Here, we evaluate the change in autophagic activity in response to O-GlcNAcylation and explore the potential mechanisms. METHODS: O-GlcNAcylation levels in bladder cancer cells were altered through pharmacological or genetic manipulations: treating with 6-diazo-5-oxo-norleucine (DON) or thiamet-G (TG) or up- and downregulation of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA). Autophagy was determined using fluorescence microscopy and western blotting. Co-immunoprecipitation (Co-IP) assays were performed to evaluate whether the autophagy regulator AMP-activated protein kinase (AMPK) was O-GlcNAc modified. RESULTS: Cellular autophagic flux was strikingly enhanced as a result of O-GlcNAcylation suppression, whereas it decreased at high O-GlcNAcylation levels. Phosphorylation of AMPK increased after the suppression of O-GlcNAcylation. We found that O-GlcNAcylation of AMPK suppressed the activity of this regulator, thereby inhibiting ULK1 activity and autophagy. CONCLUSION: We characterized a new function of O-GlcNAcylation in the suppression of autophagy via regulation of AMPK. GRAPHICAL ABSTRACT: Blockage of O-linked GlcNAcylation induces AMPK dependent autophagy in bladder cancer cells.	bladder
Type 2 diabetes mellitus predicts worse outcomes in patients with high-grade T1 bladder cancer receiving bacillus Calmette-Guérin after transurethral resection of the bladder tumor.	OBJECTIVES: The aim of this multicenter study was to investigate the prognostic role of type 2 diabetes mellitus (T2DM) comorbidity in a large multi-institutional cohort of patients with primary T1HG/G3 non-muscle-invasive bladder cancer (NMIBC) treated with transurethral resection of the bladder (TURB). MATERIALS AND METHODS: A total of 1,172 patients with primary T1 HG/G3 who had NMIBC on re-TURB and who received adjuvant intravesical bacillus Calmette-Guérin therapy with maintenance were included. Endpoints were recurrence-free survival and progression-free survival. RESULTS: A total of 231 (19.7%) of patients had T2DM prior to TURB. Five-year recurrence-free survival estimates were 12.5% in patients with T2DM compared to 36% in patients without T2DM, P < 0.0001. Five-year PFS estimates were 60.5% in patients with T2DM compared to 70.2% in patients without T2DM, P = 0.003. T2DM was independently associated with disease recurrence (hazard ratio = 1.41; 95% confidence interval = 1.20-1.66, P < 0.001) and progression (hazard ratio = 1.27; 95% confidence interval = 0.99-1.63, P < 0.001), after adjusting for other known predictive factors such as tumor size, multifocality, T1G3 on re-TURB, body mass index, lymphovascular invasion, and neutrophil-to-lymphocytes ratio. CONCLUSIONS: Given the potential implications for management, prospective validation of this finding along with translational studies designed to investigate the underlying biology of such an association are warranted.	bladder
Adherence to guideline recommendations for multimodality treatment of patients with pT2-3 M0 non-urothelial carcinoma of the urinary bladder: Temporal trends and survival outcomes.	OBJECTIVES: To analyze contemporary multimodality treatment rates, defined as radical cystectomy plus chemotherapy and/or radiotherapy, for pT2-3 any N-stage M0 non-urothelial carcinoma of urinary bladder patients. Additionally, we tested for the effect of multimodality treatment versus radical cystectomy alone on cancer-specific mortality. METHODS: Within the Surveillance, Epidemiology and End Results database (2004-2015), 887 pT2-3 any N-stage M0 non-urothelial carcinoma of urinary bladder patients treated with radical cystectomy were identified. Kaplan-Meier plots, and univariable and multivariable Cox regression analyses focused on cancer-specific mortality rates. RESULTS: Squamous cell carcinoma was recorded in 499 (56.3%) patients, neuroendocrine carcinoma in 246 (27.7%) and adenocarcinoma in 142 (16.0%). The highest proportion of multimodality treatment patients was recorded in neuroendocrine carcinoma (69.1%), relative to adenocarcinoma (34.5%) and squamous cell carcinoma (26.4%). A statistically significant annual increase was recorded in multimodality treatment rates in neuroendocrine carcinoma patients (46.7-74.2%, P < 0.01), but not in adenocarcinoma or squamous cell carcinoma patients. The 5-year cancer-specific mortality rate in neuroendocrine carcinoma patients was significantly lower after multimodality treatment versus radical cystectomy alone (37.0% vs 51.5%; P < 0.01), but no statistically significant differences were recorded in both adenocarcinoma (46.1% vs 35.5%; P = 0.8) and squamous cell carcinoma (41.4% vs 31.1%; P = 0.8) patients. In multivariable analyses, for neuroendocrine carcinoma patients, multimodality treatment was an independent predictor of a lower cancer-specific mortality rate (hazard ratio 0.58, P = 0.03). CONCLUSIONS: Multimodality treatment has been increasingly used during the study period in neuroendocrine carcinoma patients, and it has translated into a cancer-specific mortality benefit. This is not the case for other non-urothelial carcinoma of urinary bladder patients, such as adenocarcinoma or squamous cell carcinoma.	bladder
Clinical Practice Guidelines for Bladder Cancer 2019 edition by the Japanese Urological Association: Revision working position paper.	"The Clinical Practice Guidelines for Bladder Cancer edited by the Japanese Urological Association were first published in 2009 and a revised edition was released in 2015. Four years has passed since the 2015 edition, and the clinical practice environment surrounding bladder cancer has drastically changed during that time. The main changes include: (i) insurance coverage of a new diagnostic method for non-muscle-invasive bladder cancer; (ii) insurance coverage of an immune checkpoint inhibitor in advanced and metastatic bladder cancer; and (iii) advances in robot-assisted radical cystectomy as a minimally invasive treatment for muscle-invasive bladder cancer. A paradigm shift in bladder cancer diagnosis and treatment is occurring day by day. Therefore, in this 2019 edition, while dealing with the above changes, we carefully selected clinical questions with clear evidence and included other clinically important points in the general statement. We also added a new chapter on rare cancers of the urinary tract. As a new method for the evaluation of study evidence level, we introduce ""The Grading of Recommendations Assessment, Development and Evaluation"" system modified to Japanese by the Medical Information Network Distribution Service."	bladder